Streptococcus mutans (S. mutans) has been implicated as the primary etiological bacteria causing dental caries in human. S. mutans expresses a surface protein, designated as antigen I/II, B, P1, or PAc. PAc is involved in the initial adherence of S. mutans to tooth surface and the later aggregation of S. mutans on the tooth surface; thus PAc is considered a crucial virulence factor, contributing to the pathogenesis of dental caries. Due to its importance in the cariogenicity of S. mutans, PAc is recognized as a target for development of anti-caries vaccines.
Streptococcus mutans (S. mutans) has been implicated as the primary etiological bacteria causing dental caries in human. S. mutans expresses a surface protein, designated as antigen I/II, B, P1, or PAc. PAc is involved in the initial adherence of S. mutans to tooth surface and the later aggregation of S. mutans on the tooth surface; thus PAc is considered a crucial virulence factor, contributing to the pathogenesis of dental caries. Due to its importance in the cariogenicity of S. mutans, PAc is recognized as a target for development of anti-caries vaccines.
In one early study, Lehner et al. (Immunization with Purified Protein Antigens from Streptococcus mutans Against Dental Caries in Rhesus Monkeys. Infection and Immunity 34, 407-415 (1981)) had purified protein antigens I, I/II, II, and III from bacterial culture directly. The purified antigens were intramuscularly administered with adjuvant (Freund incomplete adjuvant or aluminum hydroxide). Antigens I, I/II and, to a lesser extent, antigen II induced significant reductions in dental caries, but thre was no reduction in caries with antigen III. Protection against caries was associated predominantly with serum and gingival crevicular fluid IgG antibodies. Under the immunization schemes used in this study, serum IgA antibodies showed titers of between log2 0.7 and 2.8. However, the purities of the antigens used in the experiments were in question. In addition, the claimed effectiveness might be attributed to the administration route—intramuscular.
Due to the infection mode of S. mutans, mucosal immunity shall be preferable for developing an effective vaccine. Unfortunately, numerous studies have shown that PAc without an appropriate adjuvant is a weak immunogen when given via the mucosal routes. In order to address this, Saito et al. (Protective Immunity to Streptococcus mutans Induced by Nasal Vaccination with Surface Protein Antigen and Mutant Cholera Toxin Adjuvant. Journal of Infectious Diseases 183, 823-826 (2001)) purified PAc from the cultural supernatant of S. mutans. Nasal administration of FAc and mutant cholera toxin (mCT) induced PAc-specific IgA antibodies with the titers in saliva (log 2, 6.1+/−1.7) and in nasal wash samples (log 2, 8.2+/−1.5). Ag-specific immune responses induced by nasal immunization with PAc with mCT provided significant inhibition of colonization of S. mutans. However, this study has critical shortcomings. First, the antigen PAc used was not an expressed recombinant protein; direct purification from bacterial cultures could not rule out the possibility that the shown effectiveness resulted from the contamination; this is similar to Lehner study described above. Second, cholera toxin (CT) is toxic; although it has been studied for many years, it is still far away from human uses. Finally, the effectiveness of protection against dental caries was not directly shown.
In summary, while the prior arts have indicated that PAc might be a possible antigen for developing vaccines against the dental caries caused by S. mutans, there is no teaching or suggestion of what an effective mucosal vaccine against the dental caries caused by S. mutans should be.
Therefore, there is an imperative need to develop an effective mucosal vaccine against the dental caries caused by S. mutans. 